DOI: 10.1111/j.1471-4159.1991.tb06427.x. Characterization of a Novel Serotonin Receptor Subtype (5‐HT<sub>ls</sub>) in Rat CNS: Interaction with a GTP Binding Protein

Characterization of a Novel Serotonin Receptor Subtype (5‐HTls) in Rat CNS: Interaction with a GTP Binding Protein

10.1111/j.1471-4159.1991.tb06427.x

Crossref journal-article

Wiley

Journal of Neurochemistry (311)

Abstract

AbstractThree pharmacologically distinct high‐affinity [3H]serotonin ([3H]5‐HT) binding sites were identified in spinal cord synaptosomes. [3H]5‐HT competition studies using selective 5‐HT1A receptor ligands indicated that ∼25% of high‐affinity synaptosomal [3H]5‐HT binding was inhibited by 5‐HT1A‐selective compounds, an estimate consistent with [3H](±)‐8‐hydroxy‐2‐(di‐n‐propylamino)tetralin([3H]8‐OH‐DPAT) saturation experiments in which 5‐HT1A receptors were directly labeled. [3H]5‐HT competition studies using high‐affinity 5‐HT1B compounds performed in the presence of 100 nM 8‐OH‐DPAT (to block 5‐HT1A receptors) indicated that∼26% of all specific, high‐affinity [3H]5‐HT binding to spinal cord synaptosomes was to 5‐HT1B receptors. [3H]5‐HT competition studies performed in the presence of 100 nM 8‐OH‐DPAT and 10 nM RU 24969 (to block 5‐HT1A and 5‐HT1B receptors, respectively) indicated that the remaining 49% of [3H]5‐HT binding did not possess the phar‐macologic profile previous reported for 5‐HT1c, 5‐HT1D, 5‐ HT1E, 5‐HT2, or 5‐HT3 receptors. This residual 49% of [3H]5‐ HT binding to spinal cord synaptosomes observed in the presence of 100 nM 8‐OH‐DPAT and 10 nM RU 24969 (subsequently referred to as “5‐HTls”) displayed high affinity and saturability (KD= 4.7 nM) in association/dissociation and saturation experiments. Addition of 300 μM GTP or the nonhydrolyzable form of GTP, 5′‐guanylylimidodiphosphate, inhibited [3H]5‐HT binding to 5‐HT1S receptors in saturation experiments by 35 and 57%, respectively, whereas ATP was without effect. [3H]5‐HT competition studies identified several 5‐HT agonists and antagonists with a high or moderately high affinity for 5‐HT1s receptors. Although 5‐HT1s receptors were the predominant 5‐HT1 receptor subtype present in spinal cord, no significant density of 5‐HT1s receptors was found in brainstem or frontal cortex.

Bibliography

Zemlan, F. P., & Schwab, E. F. (1991). Characterization of a Novel Serotonin Receptor Subtype (5âHTls) in Rat CNS: Interaction with a GTP Binding Protein. Journal of Neurochemistry, 57(6), 2092â2099. Portico.

Authors 2

Frank P. Zemlan (first)
Eileen F. Schwab (additional)

References 33 Referenced 19

10.1016/0024-3205(85)90271-1
10.1111/j.2042-7158.1988.tb05300.x
10.1016/0014-2999(88)90227-0
10.1016/0304-3940(87)90218-7
10.1016/0003-2697(72)90084-X
10.1038/305140a0
10.1111/j.1471-4159.1985.tb07155.x
10.1016/0014-2999(84)90002-5
10.1016/0014-2999(89)90472-X
{'key': 'e_1_2_2_11_1', 'volume-title': 'Serotonin and Pain', 'author': 'Hamon M.', 'year': '1991'} / Serotonin and Pain by Hamon M. (1991)
10.1111/j.1471-4159.1988.tb01176.x
10.1523/JNEUROSCI.07-03-00894.1987 / J. Neurosd. / Characterization of a novel 3H‐5‐hydroxytryptamine binding site subtype in bovine brain membranes by Hearing R. E. (1987)
10.1016/0014-2999(85)90658-2
10.1016/0304-3940(88)90592-7
10.1016/0006-8993(87)91572-1
10.1038/330746a0
{'key': 'e_1_2_2_18_1', 'first-page': '301', 'article-title': '[3H]Ketanserin (R 41 468), a selective 3H‐ligand for serotonin2 receptor binding sites', 'volume': '21', 'author': 'Leysen J. E.', 'year': '1982', 'journal-title': 'Mol. Pharmacol.'} / Mol. Pharmacol. / [3H]Ketanserin (R 41 468), a selective 3H‐ligand for serotonin2 receptor binding sites by Leysen J. E. (1982)
10.1016/0165-0270(85)90035-4
10.1111/j.1471-4159.1983.tb04749.x
10.1016/0028-3908(88)90198-0
10.1016/S0197-4580(89)80016-8
{'issue': '546', 'key': 'e_1_2_2_23_1', 'article-title': 'Autoradiographic mapping of serotonin receptors in rat spinal cord. (Abstr', 'volume': '15', 'author': 'Murphy R. M.', 'year': '1989', 'journal-title': 'Soc. Neurosd. Abstr.'} / Soc. Neurosd. Abstr. / Autoradiographic mapping of serotonin receptors in rat spinal cord. (Abstr by Murphy R. M. (1989)
{'key': 'e_1_2_2_24_1', 'first-page': '1333', 'article-title': 'Immunocytochemical evidence for a serotonergic in‐nervation of dorsal column postsynaptic neurons in cat and monkey: light‐ and electron‐microscopic observations', 'volume': '10', 'author': 'Nishikawa N.', 'year': '1983', 'journal-title': 'Neuro-science'} / Neuro-science / Immunocytochemical evidence for a serotonergic in‐nervation of dorsal column postsynaptic neurons in cat and monkey: light‐ and electron‐microscopic observations by Nishikawa N. (1983)
10.1016/0006-8993(85)90856-X
10.1111/j.1471-4159.1986.tb04532.x
10.1111/j.1471-4159.1986.tb12926.x
10.1038/316126a0
{'key': 'e_1_2_2_29_1', 'first-page': '480', 'article-title': 'Determination of selective and nonselective compounds for the 5‐HTIA and 5‐HT1B receptor subtypes in rat frontal cortex', 'volume': '231', 'author': 'Sills M. A.', 'year': '1984', 'journal-title': 'J. Pharmacol. Exp. Ther.'} / J. Pharmacol. Exp. Ther. / Determination of selective and nonselective compounds for the 5‐HTIA and 5‐HT1B receptor subtypes in rat frontal cortex by Sills M. A. (1984)
10.1523/JNEUROSCI.06-12-03474.1986 / J. Neurosd. / Quantitative autoradiography of multiple 5‐HT1 receptor subtypes in the brain of control and 5,7‐dihydroxytryptamine‐treated rats by Verge D. (1986)
10.1016/0014-2999(88)90825-4
{'key': 'e_1_2_2_32_1', 'first-page': '477', 'article-title': 'Spinal serotonin (5‐HT) receptor subtypes and nociception', 'volume': '226', 'author': 'Zemlan F. P.', 'year': '1983', 'journal-title': 'J. Pharmacol. Exp. Ther.'} / J. Pharmacol. Exp. Ther. / Spinal serotonin (5‐HT) receptor subtypes and nociception by Zemlan F. P. (1983)
{'key': 'e_1_2_2_33_1', 'first-page': '351', 'volume-title': 'Progress in Brain Research. Vol. 77', 'author': 'Zemlan F. P.', 'year': '1988'} / Progress in Brain Research. Vol. 77 by Zemlan F. P. (1988)
10.1016/0197-0186(90)90010-Q

Dates

Type	When
Created	18 years, 10 months ago (Oct. 5, 2006, 10:17 p.m.)
Deposited	1 year, 10 months ago (Oct. 23, 2023, 4 a.m.)
Indexed	1 year, 10 months ago (Oct. 24, 2023, 11:31 a.m.)
Issued	33 years, 9 months ago (Dec. 1, 1991)
Published	33 years, 9 months ago (Dec. 1, 1991)
Published Online	18 years, 10 months ago (Oct. 5, 2006)
Published Print	33 years, 9 months ago (Dec. 1, 1991)

Funders 0

None

BibTeX

@article{Zemlan_1991, title={Characterization of a Novel Serotonin Receptor Subtype (5‐HTls) in Rat CNS: Interaction with a GTP Binding Protein}, volume={57}, ISSN={1471-4159}, url={http://dx.doi.org/10.1111/j.1471-4159.1991.tb06427.x}, DOI={10.1111/j.1471-4159.1991.tb06427.x}, number={6}, journal={Journal of Neurochemistry}, publisher={Wiley}, author={Zemlan, Frank P. and Schwab, Eileen F.}, year={1991}, month=dec, pages={2092–2099} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2023,
        10,
        24
      ]
    ],
    "date-time": "2023-10-24T15:31:58Z",
    "timestamp": 1698161518267
  },
  "reference-count": 33,
  "publisher": "Wiley",
  "issue": "6",
  "license": [
    {
      "start": {
        "date-parts": [
          [
            2006,
            10,
            5
          ]
        ],
        "date-time": "2006-10-05T00:00:00Z",
        "timestamp": 1160006400000
      },
      "content-version": "vor",
      "delay-in-days": 5422,
      "URL": "http://onlinelibrary.wiley.com/termsAndConditions#vor"
    }
  ],
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        1991,
        12
      ]
    ]
  },
  "abstract": "<jats:title>Abstract</jats:title><jats:p>Three pharmacologically distinct high\u2010affinity [<jats:sup>3</jats:sup>H]serotonin ([<jats:sup>3</jats:sup>H]5\u2010HT) binding sites were identified in spinal cord synaptosomes. [<jats:sup>3</jats:sup>H]5\u2010HT competition studies using selective 5\u2010HT<jats:sub>1A</jats:sub> receptor ligands indicated that \u223c25% of high\u2010affinity synaptosomal [<jats:sup>3</jats:sup>H]5\u2010HT binding was inhibited by 5\u2010HT<jats:sub>1A</jats:sub>\u2010selective compounds, an estimate consistent with [<jats:sup>3</jats:sup>H](\u00b1)\u20108\u2010hydroxy\u20102\u2010(di\u2010<jats:italic>n</jats:italic>\u2010propylamino)tetralin([<jats:sup>3</jats:sup>H]8\u2010OH\u2010DPAT) saturation experiments in which 5\u2010HT<jats:sub>1A</jats:sub> receptors were directly labeled. [<jats:sup>3</jats:sup>H]5\u2010HT competition studies using high\u2010affinity 5\u2010HT<jats:sub>1B</jats:sub> compounds performed in the presence of 100 n<jats:italic>M</jats:italic> 8\u2010OH\u2010DPAT (to block 5\u2010HT<jats:sub>1A</jats:sub> receptors) indicated that\u223c26% of all specific, high\u2010affinity [<jats:sup>3</jats:sup>H]5\u2010HT binding to spinal cord synaptosomes was to 5\u2010HT<jats:sub>1B</jats:sub> receptors. [<jats:sup>3</jats:sup>H]5\u2010HT competition studies performed in the presence of 100 n<jats:italic>M</jats:italic> 8\u2010OH\u2010DPAT and 10 n<jats:italic>M</jats:italic> RU 24969 (to block 5\u2010HT<jats:sub>1A</jats:sub> and 5\u2010HT<jats:sub>1B</jats:sub> receptors, respectively) indicated that the remaining 49% of [<jats:sup>3</jats:sup>H]5\u2010HT binding did not possess the phar\u2010macologic profile previous reported for 5\u2010HT<jats:sub>1c</jats:sub>, 5\u2010HT<jats:sub>1D</jats:sub>, 5\u2010 HT<jats:sub>1E</jats:sub>, 5\u2010HT<jats:sub>2</jats:sub>, or 5\u2010HT<jats:sub>3</jats:sub> receptors. This residual 49% of [<jats:sup>3</jats:sup>H]5\u2010 HT binding to spinal cord synaptosomes observed in the presence of 100 n<jats:italic>M</jats:italic> 8\u2010OH\u2010DPAT and 10 nM RU 24969 (subsequently referred to as \u201c5\u2010HT<jats:sub>ls</jats:sub>\u201d) displayed high affinity and saturability (K<jats:sub>D</jats:sub>= 4.7 n<jats:italic>M</jats:italic>) in association/dissociation and saturation experiments. Addition of 300 <jats:italic>\u03bcM GTP</jats:italic> or the nonhydrolyzable form of GTP, 5\u2032\u2010guanylylimidodiphosphate, inhibited [<jats:sup>3</jats:sup>H]5\u2010HT binding to 5\u2010HT<jats:sub>1S</jats:sub> receptors in saturation experiments by 35 and 57%, respectively, whereas ATP was without effect. [<jats:sup>3</jats:sup>H]5\u2010HT competition studies identified several 5\u2010HT agonists and antagonists with a high or moderately high affinity for 5\u2010HT<jats:sub>1s</jats:sub> receptors. Although 5\u2010HT<jats:sub>1s</jats:sub> receptors were the predominant 5\u2010HT<jats:sub>1</jats:sub> receptor subtype present in spinal cord, no significant density of 5\u2010HT<jats:sub>1s</jats:sub> receptors was found in brainstem or frontal cortex.</jats:p>",
  "DOI": "10.1111/j.1471-4159.1991.tb06427.x",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2006,
        10,
        6
      ]
    ],
    "date-time": "2006-10-06T02:17:35Z",
    "timestamp": 1160101055000
  },
  "page": "2092-2099",
  "source": "Crossref",
  "is-referenced-by-count": 19,
  "title": "Characterization of a Novel Serotonin Receptor Subtype (5\u2010HT<sub>ls</sub>) in Rat CNS: Interaction with a GTP Binding Protein",
  "prefix": "10.1111",
  "volume": "57",
  "author": [
    {
      "given": "Frank P.",
      "family": "Zemlan",
      "sequence": "first",
      "affiliation": []
    },
    {
      "given": "Eileen F.",
      "family": "Schwab",
      "sequence": "additional",
      "affiliation": []
    }
  ],
  "member": "311",
  "published-online": {
    "date-parts": [
      [
        2006,
        10,
        5
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_2_2_2_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0024-3205(85)90271-1"
    },
    {
      "key": "e_1_2_2_3_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1111/j.2042-7158.1988.tb05300.x"
    },
    {
      "key": "e_1_2_2_4_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0014-2999(88)90227-0"
    },
    {
      "key": "e_1_2_2_5_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0304-3940(87)90218-7"
    },
    {
      "key": "e_1_2_2_6_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0003-2697(72)90084-X"
    },
    {
      "key": "e_1_2_2_7_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/305140a0"
    },
    {
      "key": "e_1_2_2_8_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1111/j.1471-4159.1985.tb07155.x"
    },
    {
      "key": "e_1_2_2_9_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0014-2999(84)90002-5"
    },
    {
      "key": "e_1_2_2_10_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0014-2999(89)90472-X"
    },
    {
      "key": "e_1_2_2_11_1",
      "volume-title": "Serotonin and Pain",
      "author": "Hamon M.",
      "year": "1991"
    },
    {
      "key": "e_1_2_2_12_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1111/j.1471-4159.1988.tb01176.x"
    },
    {
      "key": "e_1_2_2_13_1",
      "doi-asserted-by": "crossref",
      "first-page": "894",
      "DOI": "10.1523/JNEUROSCI.07-03-00894.1987",
      "article-title": "Characterization of a novel 3H\u20105\u2010hydroxytryptamine binding site subtype in bovine brain membranes",
      "volume": "7",
      "author": "Hearing R. E.",
      "year": "1987",
      "journal-title": "J. Neurosd."
    },
    {
      "key": "e_1_2_2_14_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0014-2999(85)90658-2"
    },
    {
      "key": "e_1_2_2_15_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0304-3940(88)90592-7"
    },
    {
      "key": "e_1_2_2_16_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0006-8993(87)91572-1"
    },
    {
      "key": "e_1_2_2_17_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/330746a0"
    },
    {
      "key": "e_1_2_2_18_1",
      "first-page": "301",
      "article-title": "[3H]Ketanserin (R 41 468), a selective 3H\u2010ligand for serotonin2 receptor binding sites",
      "volume": "21",
      "author": "Leysen J. E.",
      "year": "1982",
      "journal-title": "Mol. Pharmacol."
    },
    {
      "key": "e_1_2_2_19_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0165-0270(85)90035-4"
    },
    {
      "key": "e_1_2_2_20_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1111/j.1471-4159.1983.tb04749.x"
    },
    {
      "key": "e_1_2_2_21_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0028-3908(88)90198-0"
    },
    {
      "key": "e_1_2_2_22_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0197-4580(89)80016-8"
    },
    {
      "issue": "546",
      "key": "e_1_2_2_23_1",
      "article-title": "Autoradiographic mapping of serotonin receptors in rat spinal cord. (Abstr",
      "volume": "15",
      "author": "Murphy R. M.",
      "year": "1989",
      "journal-title": "Soc. Neurosd. Abstr."
    },
    {
      "key": "e_1_2_2_24_1",
      "first-page": "1333",
      "article-title": "Immunocytochemical evidence for a serotonergic in\u2010nervation of dorsal column postsynaptic neurons in cat and monkey: light\u2010 and electron\u2010microscopic observations",
      "volume": "10",
      "author": "Nishikawa N.",
      "year": "1983",
      "journal-title": "Neuro-science"
    },
    {
      "key": "e_1_2_2_25_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0006-8993(85)90856-X"
    },
    {
      "key": "e_1_2_2_26_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1111/j.1471-4159.1986.tb04532.x"
    },
    {
      "key": "e_1_2_2_27_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1111/j.1471-4159.1986.tb12926.x"
    },
    {
      "key": "e_1_2_2_28_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/316126a0"
    },
    {
      "key": "e_1_2_2_29_1",
      "first-page": "480",
      "article-title": "Determination of selective and nonselective compounds for the 5\u2010HTIA and 5\u2010HT1B receptor subtypes in rat frontal cortex",
      "volume": "231",
      "author": "Sills M. A.",
      "year": "1984",
      "journal-title": "J. Pharmacol. Exp. Ther."
    },
    {
      "key": "e_1_2_2_30_1",
      "doi-asserted-by": "crossref",
      "first-page": "3474",
      "DOI": "10.1523/JNEUROSCI.06-12-03474.1986",
      "article-title": "Quantitative autoradiography of multiple 5\u2010HT1 receptor subtypes in the brain of control and 5,7\u2010dihydroxytryptamine\u2010treated rats",
      "volume": "6",
      "author": "Verge D.",
      "year": "1986",
      "journal-title": "J. Neurosd."
    },
    {
      "key": "e_1_2_2_31_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0014-2999(88)90825-4"
    },
    {
      "key": "e_1_2_2_32_1",
      "first-page": "477",
      "article-title": "Spinal serotonin (5\u2010HT) receptor subtypes and nociception",
      "volume": "226",
      "author": "Zemlan F. P.",
      "year": "1983",
      "journal-title": "J. Pharmacol. Exp. Ther."
    },
    {
      "key": "e_1_2_2_33_1",
      "first-page": "351",
      "volume-title": "Progress in Brain Research. Vol. 77",
      "author": "Zemlan F. P.",
      "year": "1988"
    },
    {
      "key": "e_1_2_2_34_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0197-0186(90)90010-Q"
    }
  ],
  "container-title": "Journal of Neurochemistry",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fj.1471-4159.1991.tb06427.x",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1471-4159.1991.tb06427.x",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2023,
        10,
        23
      ]
    ],
    "date-time": "2023-10-23T08:00:50Z",
    "timestamp": 1698048050000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.1991.tb06427.x"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        1991,
        12
      ]
    ]
  },
  "references-count": 33,
  "journal-issue": {
    "issue": "6",
    "published-print": {
      "date-parts": [
        [
          1991,
          12
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1111/j.1471-4159.1991.tb06427.x"
  ],
  "URL": "http://dx.doi.org/10.1111/j.1471-4159.1991.tb06427.x",
  "relation": {},
  "ISSN": [
    "0022-3042",
    "1471-4159"
  ],
  "subject": [],
  "container-title-short": "Journal of Neurochemistry",
  "published": {
    "date-parts": [
      [
        1991,
        12
      ]
    ]
  }
}